Reaction-Driven Assembly and Diffusiophoresis: Mechanisms for Control and Organization of Life-like Systems
by Gregor Häfner
Date of Examination:2024-05-06
Date of issue:2024-07-12
Advisor:Prof. Dr. Marcus Müller
Referee:Prof. Dr. Marcus Müller
Referee:Prof. Dr. Stefan Klumpp
Referee:Prof. Dr. Timo Betz
Referee:Dr. Peter Keim
Referee:Dr. David Zwicker
Referee:Prof. Dr. Matthias Krüger
Persistent Address:
http://dx.doi.org/10.53846/goediss-10606
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Abstract
English
The interior of cells, a fundamental building block of biological systems, is a hetero- geneous environment comprised of a multitude of molecular species. Its organization in the form of aggregates and compartments is tightly bound to the cellular function and demands precise coordination, positioning, and transportation. To achieve this, bi- ological systems operate in non-equilibrium, dissipating energy and exporting entropy to the exterior. Driven chemical reactions, wherein molecules of high internal energy are consumed, are one way to achieve this. In such a scenario, the formation and shape of membraneless organelles, characterized as phase-separated fluid condensates, result from an interplay of phase separation and chemical reactions that drive the system out of equilibrium. In addition to this, the properties of membrane-bound organelles, com- partments that are surrounded by an amphiphilic bilayer, may be influenced away from equilibrium, granting cells control over their topologies. This dissertation is dedicated to the question how driven chemical reactions influence the dynamics of biologically inspired systems. In particular, what are the properties and dynamics of aggregates formed from amphiphilic molecules, which are dynami- cally produced within a chemical reaction cycle? And how do long-range concentra- tion gradients that emerge from locally and externally replenished reactants influence the positioning and growth of condensates, both with and without membranes? Theoretical concepts from polymer physics are employed to answer these questions. To this end, a software is developed that simulates the time evolution of concentra- tion fields within a continuum model. The implementation is kept flexible and allows the blending of arbitrary numbers of diblock copolymer and homopolymer species. It makes efficient use of modern GPUs, which facilitates the investigation of large length and time scales. As a complementary simulation scheme, particle-based simulations are employed, wherein the reactions are implemented either as type conversions of en- tire macromolecules or as the conversion of monomeric units. Firstly, the reaction-driven assembly of molecules, that are switched between a hy- drophilic and an amphiphilic state within a reaction cycle, is investigated. Such systems could be implemented synthetically or may have played a role prebiotically. Both the- oretical considerations within the continuum model and simulations are used to study the initial dynamics of structure formation and, assuming instantaneous fuel recov- ery in the system, nonequilibrium steady states are identified. Aggregates may stack in lattices and the reaction rates influence the lattice spacing. Since the amphiphiles’ architecture dictates the membrane thickness in equilibrium, there is an interplay of length scales – the reaction-dictated lattice spacing and the membrane thickness. To- gether, these determine the membrane topology in the steady state. Theoretically, the membrane thickness is found to be approximately unaltered by the chemical reactions. Nonetheless, we show in the simulations, that compartments that form in the process, closed vesicles, accumulate precursor material which imparts tension on the membrane and decreases the membrane thickness. For certain parameter regions, this may even stabilize the formation of pores in the vesicles, which are propelled by the efflux of pre- cursor in opposite direction of the pore. Chemical reactions hence serve as a means to alter and control membrane topologies. Secondly, a strategy for cells to organize intra-cellular condensates via reaction-driven diffusiophoresis is demonstrated. In its original context, diffusiophoresis refers to the movement of hard colloids in external concentration gradients. Here, it is shown that passive liquid droplets are also transported in an external concentration gradient, be- cause the external component maintains a finite flux inside the droplet, depending on the interactions. Incompressibility in turn dictates a droplet flux in the opposite direc- tion, which induces the motion. This effect occurs naturally in systems with a reac- tion cycle that is driven by the conversion of high-internal-energy molecules, termed fuel, into a state of low internal energy, termed waste. To continuously enable the re- action cycle, fuel needs to be locally replenished and waste locally drained. In this case, fuel and waste concentrations exhibit gradients, such that dynamically emerging droplets are driven to or away from sources and sinks, depending on their interactions with fuel and waste. Theoretical considerations reveal an additional contribution to the movement of droplets that stems from an asymmetry in production in the droplets’ surroundings. In addition, it is explicitly shown that droplets with different composi- tions and distinct interactions can be transported in opposite directions simultaneously. Therefore, the phenomenon serves as a precise tool for biological systems to selectively position and move aggregates. Finally, the concept of reaction-driven diffusiophoresis is applied to aggregates that are assembled from amphiphilic molecules. By systematically varying molecular ar- chitectures and interactions, different pathways to form vesicles are explored. These dynamics circumvent free-energy barriers, which would emerge in their equilibrium counterpart and hamper self-assembly. More generally, there are two concepts that are common threads of these investiga- tions: Driven chemical reactions that change molecular solubility introduce a length scale, which determines phase-domain morphologies in an interplay with the system’s other intrinsic length scales. Furthermore, the investigations highlight the possibility of transport processes that originate from the dissipation of chemical energy through reaction cycles. To this end, an accurate treatment of the incompressibility constraint of typical aqueous solutions is essential.
Keywords: Reaction-driven Assembly; Diffusiophoresis; Simulation; Polymer Physics; Membraneless Organelles; Vesicles
